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1. The dynamics of the ventilatory response to carbon dioxide inhalation were studied in ten healthy young men using four different inspired fractions of carbon dioxide (FI, CO2) in air (0.015, 0.030, 0.045 and 0.060) successively increasing and decreasing stepwise. 2. Seven such different progressions were performed for each subject and each of seven different durations of the steps (t) ranging between 0.1 (i.e. one ventilatory cycle) and 10 min ('steady-state' conditions). The overall duration of one test (T) was taken as the sum of the seven successive FI, CO2 steps (t) plus one step, t, of air breathing. Thus, the values of T ranged between 0.8 (i.e. eight ventilatory cycles) and 80 min. Three subjects were tested twice. 3. We measured, as a function of T, the magnitude of the loops formed by the curves PA, CO2-VE and the value of the highest ventilatory response (VE max) to each progression. For all ten subjects, both functions had two maxima, one for T values of 2.6 or 8.0 min and one for T values of 24 or 40 min, and one minimum at T equal to 12 min. 4. The same measurements were made on tidal volume-response curves (PA, CO2-VT) and ventilatory frequency-response curves (PA, CO2-f) and yielded the same results except for the ventilatory frequency-response curves, for which we only found a statistically insignificant single maximum for T values of 24 or 40 min. 5. The locations of the maxima in loop magnitude and VE max were similar in duplicate tests in three subjects, whereas the quantitative values of these variables showed wide differences. 6. We compared our results with what is expected from the current linear dynamic model of ventilatory control submitted to the same forcing function: the first maximum in the loop magnitude is predicted by the model, but the second is not. The model shows no peak in the evolution of VE max. 7. We conclude that controlled system dynamics, which are the only ones included in dynamic models of ventilatory control, cannot by themselves account for our observations, and that one should take into consideration the dynamics of the controlling neuronal network.

SUMMARY1. The dynamics of the ventilatory response to isocapnic hypoxia were studied in seven healthy subjects using four different levels of hypoxia, (inspired oxygen pressures, P1I02 equal to 110, 100, 80 and 60 mmHg) successively increasing and decreasing stepwise.2. Five such progressions were performed for each subject, corresponding to five different durations of the steps (t) ranging between 0 33 and 5 00 min. The overall duration of one test (T) was taken as the sum of the seven successive P10 2 hypoxic steps (t) plus one step t of air breathing. Thus, the values of T ranged between 2-6 and 40 0 min.3. End-tidal CO2 pressure was maintained constant (±1 mmHg) throughout the test by manipulation of inspired CO2 pressure.4. We measured, as a function of T, (i) the magnitude of the loops formed by the ventilatory response curves (PAo2-VE) as measured by their surface area (S),(ii) the magnitude of ventilatory response to each rising hypoxic step, and (iii) the difference between resting VE and VE observed at PA, 2 equal to 50 mmHg (AV50).On average, we found one maximum in absolute value of S at T = 8 min and one minimum at T = 12 min, along with two maxima of ventilatory response at T values of 8 and 24 min.5. The same measurements were made on tidal volume response curves (PA,2 -VT) and ventilatory frequency response curves (PA, 2-f): on average we observed two non-significant peaks in the progression with T of VT and S(VT) and two significant peaks in that of AVT,50 for T = 8 and T = 24 min. No significant peak was observed in the progression with T of f curve parameters.6. These results are discussed together with the current dynamic model of the ventilatory control system, which includes a central neural controller with no dynamics of its own and a linear response to chemoreceptor inputs. We discuss the physiological meaning of a negative loop area in relation to the previously described depressant effect of hypoxia upon the brain stem. 7. We conclude that the dynamics of the controlling neuronal network are responsible for the observed singularities which result from differential sensitivity J. F. BERTHOLON AND OTHERS properties of the controller. We propose the existence of discrete excitatory states of the controller as a possible explanation of the shape of the steady-state response curve to hypoxia and of the loop variations.

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